Significance Gut-associated lymphoid tissue (GALT) is an important site for early viral replication and dissemination and severe CD4+ T cell depletion. These changes are not adequately reflected in peripheral blood or lymph nodes. GALT will be valuable in determining mechanisms of SIV-associated CD4+ T cell depletion. Objectives The present study was performed to examine the kinetics of viral replication and CD4+ T cell depletion in GALT in comparison with peripheral blood and lymph nodes during the course of SIV infection in rhesus macaques. Results Viral replication and severe CD4+ T cell depletion occurred in GALT during primary SIV infection in rhesus macaques. This was accompanied by an increase in intestinal CD8+ T cell percentages and increased potential of expression of Th1 type cytokines. These changes could reflect altered T cell homeostasis in GALT and play an important role in SIV-associated enteropathy and viral pathogenesis. Future Directions Future studies will focus on determining the mechanisms of SIV-associated CD4+ T cell depletion in GALT. Studies of anti-retroviral therapy of SIV-infected macaques will be performed to determine the mechanisms of CD4+ T cell repopulation and viral suppression in GALT. KEY WORDS gut-associated, lymphoid tissue, viral replication, SIV FUNDING NIH Grant AI043274 PUBLICATIONS Smit-McBride, Z., Mattapallil, J., McChesney, M., Ferrick, D. and Dandekar, S. Journal of Virology 72:6646-6656, 1998. Mattapallil, J, Smit-McBride Z, McChesney, M, and Dandekar, S. Journal of Virology 72:6421-6429, 1998. Smit-McBride, Z, Mattapallil, J., Villinger, F., Ansari A, Dandekar, S. Jounal of Medical Primatology 27:129-140, 1998.